Heart failure is complex, but at its core, it results in a reduced ability of the heart to fill with blood and then pump it throughout the body. The pump function of the whole heart is driven by the ability of millions of heart cells (myocytes) to contract with every heart beat. Inside each of these cells is a specialized protein lattice called the myofilament, which is what actually causes myocytes, and the heart, to contract.

The Kirk lab uses sophisticated biophysical assays to study human and animal models of disease to understand the precise molecular mechanisms that cause the myofilament to malfunction. Myofilament function is exquisitely controlled by switches (called post-translational modifications, PTMs) on the proteins that make up the lattice, and we use mass spectrometry to discover which of these have been incorrectly switched on (or off) in disease. Then we determine how to reverse these switches and attempt to restore contractile strength to the heart.